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Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene

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Abstract

There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse K-ras gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T>A, rs12226937: G>A, and rs61761074: T>G) located in the same region of human KRAS. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G>A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T>G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.

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Acknowledgements

The research has been carried out with support of the grant from Russian Academy of Science Program Fundamental Science for Medicine #23, and Federal Targeted Programmer for Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014-2020, Development of Molecular Signatures for Early Detection of Lung Cancer (No. 14.575.21.0064 from 05.08.2014) and State Budget Project N VI.58.1.2.

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Lavrentieva avenue 10, Novosibirsk, 630090, Russian Federation

    Elena V Antontseva, Marina Yu Matveeva, Natalia P Bondar, Elena V Kashina, Elena Yu Leberfarb, Leonid O Bryzgalov, Yury L Orlov & Tatiana I Merkulova

  2. Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation

    Yury L Orlov & Tatiana I Merkulova

  3. Tomsk Cancer Research Institute, Kooperativny Lane 5, Tomsk, 634050, Russian Federation

    Polina A Gervas, Anastasia A Ponomareva & Nadezhda V Cherdyntseva

  4. Tomsk Polytechnical University, Lenina Avenue, 32, Tomsk, 634050, Russian Federation

    Anastasia A Ponomareva

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  1. Elena V Antontseva
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  2. Marina Yu Matveeva
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  3. Natalia P Bondar
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  4. Elena V Kashina
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  6. Leonid O Bryzgalov
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  7. Polina A Gervas
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  8. Anastasia A Ponomareva
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  9. Nadezhda V Cherdyntseva
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  10. Yury L Orlov
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  11. Tatiana I Merkulova
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Correspondence to Marina Yu Matveeva.

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Corresponding editor: Sorab N Dalal

[Antontseva EV, Matveeva MY, Bondar NP, Kashina EV, Leberfarb EY, Bryzgalov LO, Gervas PA, Ponomareva AA, Cherdyntseva NV, Orlov YL and Merkulova TI 2015 Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene. J. Biosci.] DOI 10.1007/s12038-015-9567-8

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Antontseva, E.V., Matveeva, M.Y., Bondar, N.P. et al. Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene. J Biosci 40, 873–883 (2015). https://doi.org/10.1007/s12038-015-9567-8

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